Cancer is the leading nontraumatic cause of death among young adults. In individuals under age 40, cancer has a distinct biology and often has an underlying genetic etiology. However, consensus guidelines driven by phenotypic characteristics fail to identify many young adult patients with inherited genetic risk, in part due to their complexity and to lack of data on mutation frequency. We likely vastly underestimate the frequency and spectrum of germline susceptibility in young adults with cancer, knowledge of which would have far-reaching implications both for their treatment and follow-up care and for the diagnosis and management of relatives. Thus, better strategies for diagnosing inherited risk among young adults with cancer are needed. Further, genetic testing rates among relatives of those identified with inherited cancer risk range from 50-60%; interventions to overcome the barriers that patients and relatives face, so they can take appropriate screening and risk-reducing measures, must be developed and tested. Finally, there is a critical need to integrate genetic evaluation and test results into the electronic medical record (EMR) to facilitate tailored clinical decision support for both clinicians and patients. The present proposal seeks to overcome the limitations of current data and models of care through two Specific Aims. First, we will conduct a randomized controlled trial among 1421 young adults with cancer, one-third of whom will be members of racial or ethnic minorities or medically underserved groups, to compare rates of ascertainment of genetic risk between guideline-driven, phenotype- directed genetic testing (current standard of care) and universal cancer panel genetic testing. Working with the Penn Medicine Nudge Unit and Information Services, we will develop EMR-based algorithms for automatic patient referral and clinical decision support, driven by discrete genetic test results ported into the EMR via HL7, that will include ?active choice? nudges, direct-to-patient alerts, and physician dashboards that minimize physician burden. We will compare adherence to screening recommendations among participants to that among historical controls. Second, we will compare the impact of the two up-front testing strategies among patients, enhanced by a novel strategy of direct team outreach to at-risk relatives, on ascertainment of genetic risk among family members. We also will conduct qualitative interviews with a diverse sample of patients, relatives, and family groups to describe the critical interactions that facilitate or impede communication about risk and cascade testing within families and to explore the acceptability of direct clinical team outreach to at- risk relatives. The proposed study promises to immediately alter national standards of care and payer policies by identifying the preferred approach to evaluating young adult cancer patients for genetic risk through a rigorous randomized trial, while measuring ascertainment among both patients and their relatives. In addition, beyond its potential to change standards of care, the study will generate shareable EMR-based code, algorithms, and models that will further enhance the sustainability of the proposed approach.